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 This is an original JCO publication from 2009. Please visit the JCO website to access the full article.


Use of Chemotherapy and Radiation Therapy Protectants


 

 Authors
Martee L. Hensley, Karen L. Hagerty, Tarun Kewalramani, Daniel M. Green, Neal J. Meropol, Todd H. Wasserman, Gary I. Cohen, Bahman Emami, William J. Gradishar, R. Brian Mitchell, J. Tate Thigpen, Andy Trotti, III, Daniel von Hoff, Lynn M. Schuchter

SUMMARY OF RECOMMENDATIONS

 

 

Recommendation Category

Recommendations

Recommendations for the Use of Dexrazoxane

Breast Cancer

Initial Use in Patients with Metastatic Breast Cancer

No change from 2002. It is recommended that dexrazoxane not routinely be used for patients with metastatic breast cancer receiving initial doxorubicin-based chemotherapy.

Delayed Use in Patients with Metastatic Breast Cancer Who Have Received More Than 300 mg/m2 of Doxorubicin

No change from 2002. It is suggested that the use of dexrazoxane be considered for patients with metastatic breast cancer who have received more than 300 mg/m2 of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy.

Management of patients who received more than 300 mg/m2 in the adjuvant setting and are now initiating doxorubicin-based chemotherapy in the metastatic setting should be individualized, with consideration given to the potential for dexrazoxane to decrease response rates, and to the risk of cardiac toxicity, and because these patients were not included in the clinical trials of dexrazoxane.

Use in Patients Receiving Adjuvant Chemotherapy for Breast Cancer

No change from 2002. The use of dexrazoxane in the adjuvant setting is not suggested outside of a clinical trial.

Other Malignancies

Use in Adult Patients With Other Malignancies

No change from 2002. The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m2 of doxorubicin-based therapy. Caution should be exercised in the use of dexrazoxane in settings in which doxorubicin-based therapy has been shown to improve survival.

Use in Pediatric Malignancies

No change from 2002. There is insufficient evidence to make a recommendation for the use of dexrazoxane in the treatment of pediatric malignancies.

Other Anthracycline Doses and Schedules

Use in Patients Receiving Other Anthracyclines or Other Anthracycline Dose Schedules

No Change from 2002. On the basis of the available data and extrapolations from the experience with doxorubicin plus dexrazoxane, the use of dexrazoxane may be considered for patients responding to anthracycline-based chemotherapy for advanced breast cancer and for whom continued epirubicin therapy is clinically indicated. Data for using dexrazoxane with epirubicin for treatment of other cancers are limited. Data are insufficient to make a recommendation regarding the use of dexrazoxane with other potentially cardiotoxic agents.

Use in Patients Receiving High-Dose Anthracycline Therapy

There are no new data addressing the use of dexrazoxane, and there are no new data regarding the clinical use of high-dose anthracyclines.  Thus, the Panel has elected to delete this particular guideline statement, since its clinical relevance appears limited.

Use in Patients With Cardiac Risk Factors

No change from 2002. There is insufficient evidence on which to base a recommendation for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease.

Monitoring Therapy

Termination of Anthracycline Therapy for Patients Receiving Dexrazoxane

No change from 2002. Patients receiving dexrazoxane should continue to undergo cardiac monitoring. After cumulative doxorubicin doses of 400 mg/m2, cardiac monitoring should be frequent. The panel suggests repeating the monitoring study after 500 mg/m2 and subsequently after every 50 mg/m2 of doxorubicin. The panel suggests that the termination of dexrazoxane/doxorubicin therapy be strongly considered in patients who develop a decline in LVEF to below institutional normal limits or who develop clinical congestive heart failure.

Dose of Dexrazoxane

No change from 2002. It is suggested that patients who are being treated with dexrazoxane receive dexrazoxane at a ratio of 10:1 with the doxorubicin dose, given by slow IV push or short IV infusion, 15 to 30 minutes before doxorubicin or epirubicin administration. A ratio of 10:1 with the epirubicin dose may be reasonable. However, it should be noted that the optimal dose ratio has not been determined.

RECOMMENDATIONS FOR THE USE OF AMIFOSTINE

Amifostine Use in Chemotherapy-Associated Toxicities

Nephrotoxicity

No change from 2002. Amifostine may be considered for the prevention of nephrotoxicity in patients receiving cisplatin-based chemotherapy.

Neutropenia

While the use of amifostine may be considered for reduction of the incidence of grade 3 and 4 neutropenia associated with chemotherapy, the clinician may reasonably consider alternative strategies such as the use of myeloid growth factor support or chemotherapy dose reduction to ameliorate neutropenia.

Thrombocytopenia

The Panel recommends against the use of amifostine for protection against thrombocytopenia in patients receiving chemotherapy or radiotherapy.

Neurotoxicity and Ototoxicity

Present data are insufficient to support the routine use of amifostine for the prevention of platinum-associated neurotoxicity or ototoxicity.

Paclitaxel-Associated Neurotoxicity

Data are insufficient to support the routine use of amifostine for the prevention of paclitaxel-associated neuropathy.

Dose and Administration of Amifostine with Chemotherapy

The current FDA-approved dose of amifostine is 910 mg/m2 intravenously over 15 minutes, 30 minutes prior to chemotherapy.  Familiarity with the package insert and close patient monitoring during the infusion are required.  Common toxicities include acute hypotension, nausea, and fatigue.

Amifostine Use in Radiation Therapy-Associated Toxicities

Xerostomia

The use of amifostine may be considered to decrease the incidence of acute and late xerostomia in patients undergoing fractionated radiotherapy alone for head and neck cancer.  Current data do not support the routine use of amifostine with concurrent platinum-based chemoradiotherapy for head and neck cancer.

Mucositis

Data are insufficient to recommend amifostine to prevent mucositis associated with radiation therapy for head and neck cancer.

Esophagitis (Note: This topic is new to the guideline)

Data are insufficient to recommend the routine use of amifostine to prevent esophagitis in patients receiving concurrent chemoradiotherapy for non-small cell lung cancer.

Dose and Administration of Amifostine With Radiation Therapy

No change from 2002. When given with radiation therapy, the recommended amifostine dose is 200 mg/m2/d, given as a slow IV push over 3 minutes, 15 to 30 minutes before each fraction of radiation therapy. Administration of amifostine requires close patient monitoring, but side effects are fewer at this lower dose. Many patients require antiemetics. Blood pressure should be measured just before and immediately after the 3-minute amifostine infusion. The hypotension associated with amifostine at this dose is less frequent but still requires close monitoring.

RECOMMENDATIONS FOR THE USE OF PALIFERMIN (Note: This topic is new to the guideline)

Autologous Hematopoietic Stem Cell Transplantation

Palifermin is recommended for use in patients undergoing autologous stem cell transplantation for a hematologic malignancy with a total body irradiation (TBI) conditioning regimen to decrease the incidence of severe mucositis.  Palifermin may be considered for use in patients whose conditioning regimens include involved-field radiotherapy to the oral cavity, oropharynx, and/or esophagus, regardless of whether the conditioning regimen includes TBI.  There are insufficient data to recommend the routine use of palifermin for patients undergoing autologous stem cell transplantation for a hematologic malignancy where the conditioning regimen is chemotherapy-only.

Allogeneic Hematopoietic Stem Cell Transplantation

Palifermin may be considered for use in patients undergoing myeloablative allogeneic hematopoietic stem cell transplant with a TBI-based conditioning regimen. There are insufficient data to recommend its use in myeloablative conditioning regimens consisting of chemotherapy alone in this setting.

Dose and Administration of Palifermin With Hematopoietic Stem Cell Transplantation

Palifermin should be administered intravenously at 60 μg/kg daily for 3 days preceding the start of the conditioning regimen and 60 μg/kg daily for 3 days beginning on the day of stem cell infusion.  It should not be administered within 24 hours of the initiation of the conditioning regimen.

Non-Stem Cell Transplantation and Solid Tumors

There are insufficient data to recommend the use of palifermin in the non-stem cell transplant setting, or for use in the treatment of solid tumors.

RECOMMENDATIONS FOR THE USE OF MESNA

Mesna Use with Ifosfamide

Mesna Dosing With Standard-Dose Ifosfamide

No change from 2002. It is suggested that the daily dose of mesna be calculated to equal 60% of the total daily dose of ifosfamide, administered as three bolus doses given 15 minutes before and 4 and 8 hours after administration of each dose of ifosfamide, when the ifosfamide dose is less than 2.0.5 g/m2/d administered as a short infusion. For use with continuous-infusion ifosfamide, mesna may be administered as a bolus dose equal to 20% of the total ifosfamide

dose followed by a continuous infusion of mesna equal to 40% of the ifosfamide dose, continuing for 12 to 24 hours after completion of the ifosfamide infusion.

Mesna Dosing With High-Dose Ifosfamide

No change from 2002. There is insufficient evidence on which to base a recommendation for the use of mesna with ifosfamide doses in excess of 2.5 g/m2/d. The efficacy of mesna for urothelial protection with very high-dose ifosfamide has not been established. Given the longer half-life of ifosfamide in these dosages, more frequent and prolonged mesna dosage regimens may be necessary for maximum protection from urotoxicity.

Mesna Administration by theOral Route

No change from 2002. Mesna tablets have been approved by the United States Food and Drug Administration (FDA) to prevent hemorrhagic cystitis in patients receiving ifosfamide chemotherapy. The recommended dose and schedule is to administer mesna as an IV bolus injection in a dosage equal to 20% of the ifosfamide dosage (weight/weight) at the time of ifosfamide administration. Mesna tablets are given orally in a dosage equal to 40% of the ifosfamide dose at 2 and 6 hours after each dose of ifosfamide. The total daily dose of mesna is 100% of the ifosfamide dose. Patients who vomit within 2 hours of taking oral mesna should repeat the dose or receive IV mesna. The dosing schedule should be repeated on each day that ifosfamide is administered.

Mesna Use With Cyclophosphamide

No change from 2002. Mesna plus saline diuresis or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide in the setting of stem-cell transplantation.

Surveillance of Patients Receiving Ifosfamide and/or Cyclophosphamide and Mesna

No change from 2002. There are insufficient data to make a recommendation regarding specific monitoring for hemorrhagic cystitis in patients receiving mesna to ameliorate ifosfamide or high-dose cyclophosphamide-associated urothelial toxicity. Recommendations for monitoring reflect the design of clinical trials involving mesna use and the opinion of the panel.

 

  • Abbreviations: LVEF, left ventricular ejection fraction; IV, intravenous; FDA, US Food and Drug Administration.

  • * This topic is new to the guideline.

 

 

 

 

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